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Increased Thyroxine Clearance in Rats Treated with High Doses of a Histamine H2-Antagonist, SKF 93479

  • C. G. Brown
  • R. F. Harland
  • C. K. Atterwill
Conference paper
Part of the Archives of Toxicology, Supplement book series (TOXICOLOGY, volume 11)

Abstract

Treatment of rats with high doses (200-1000 mg/kg) of a histamine H2-antagonist, SKF 93479 (2-(2-(5-(dimethylaminomethyl)furan-2-ylmethylthio)-furan-2-ylmethyl-amino)-5-(6-methylpyrid-3-ylmethyl)pyrimidin-4-one trihydrochloride), is associated with histological changes in the thyroid glands. These changes were observed as early as 3 days after the start of treatment, and include follicular cell hypertrophy and colloid depletion, which are indicative of increased thyroid activity. Similar thyroid histological changes have previously been observed in rats following treatment with classical antithyroid compounds such as methimazole (Owen et al. 1973). Several investigations were carried out in order to determine the mechanism of the effect of SKF 93479 on thyroid activity. In particular, the possibility of a direct or indirect effect of the compound (the latter via alterations in the pituitary feedback mechanism) was examined by studying plasma thyroxine (T4) and thyroid stimulating hormone (TSH) concentrations, thyroidal iodide-125 uptake and T4 clearance in rats treated with SKF 93479.

Keywords

Thyroid Stimulate Hormone Iodide Uptake Lateral Tail Vein Serum Thyroid Stimulate Hormone Trichloroacetic Acid Solution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Brown CG, Fowler K, Nicholls PJ, Atterwill CK (1986) Assessment of thyrotoxicity using in vitro cell culture systems. Food Chem Toxicol 24:557–562PubMedCrossRefGoogle Scholar
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  4. Tsukui T, Aizawa T, Yamada T, Kawabe T (1978) Studies on the mechanisms of goitrogenic action of diphenylhydantoin. Endocrinology 102:1662–1669PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • C. G. Brown
    • 1
  • R. F. Harland
    • 1
  • C. K. Atterwill
    • 1
  1. 1.Department of ToxicologySmith Kline and French Research Ltd.WelwynUK

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